Michael Moussouttas

Cerebrospinal Fluid Catecholamine Levels as Predictors of Outcome in Subarachnoid Hemorrhage

Objective: Subarachnoid hemorrhage (SAH) is associated with marked sympathetic activation at the time of ictus. The purpose of this study is to determine whether early central catecholamine levels measured from cerebrospinal fluid (CSF) relate to outcome in patients with SAH. Methods: Observational study of consecutive SAH grade 3–5 patients who underwent ventriculostomy placement, but did not undergo open craniotomy for aneurysm obliteration. CSF samples were obtained during the first 48 h following symptom onset and assayed for catecholamine levels. Statistical analyses were performed to determine whether the levels predicted mortality by day 15 or mortality/disability by day 30. Results: For the 102 patients included, mean age was 58, and 73% were female – 21% experienced day-15 mortality, and 32% experienced mortality/disability by day 30. Early mortality was related to Hunt-Hess (H/H) grade (p < 0.001), neurogenic cardiomyopathy (NC) (p = 0.003), cerebral infarction (p = 0.001), elevated intracranial pressure (ICP) (p = 0.029), epinephrine (EPI) level (p = 0.002) and norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p = 0.003). Mortality/disability was related to H/H grade (p < 0.001), NC (p = 0.018), infarction (p < 0.001), elevated ICP (p = 0.002), EPI (p = 0.004) and NE/DHPG (p = 0.014). Logistic regression identified age [OR 1.09 (95% CI 1.01–1.17)], H/H grade [9.52 (1.19–77)], infarction [10.87 (1.22–100)], ICP elevation [32.26 (2–500)], EPI [1.06 (1.01–1.10)], and (inversely) DHPG [0.99 (0.99–1.00)] as independent predictors of early mortality. For mortality/disability, H/H grade [OR 21.74 (95% CI 5.62–83)], ICP elevation [18.52 (1.93–166)], and EPI [1.05 (1.02–1.09)] emerged as independent predictors. Proportional-hazards analysis revealed age [HR 1.041 (95% CI 1.003–1.08)], H/H grade [6.9 (1.54–31.25)], NC [4.31 (1.5–12.35)], and EPI [1.032 (1.009–1.054)] independently predicted early mortality. Conclusions: CSF catecholamine levels are elevated in SAH patients who experience early mortality or disability. EPI may potentially serve as useful index of outcome in this population of patients with SAH.

Silent Cerebral Small Vessel Disease in Restless Legs Syndrome.

STUDY OBJECTIVES Growing literature suggests that patients with restless legs syndrome (RLS) may be at increased risk for hypertension, heart disease, and stroke. Cerebral small vessel disease (SVD) is a known risk factor for clinical stroke. This study evaluated silent cerebral SVD by MRI in patients with RLS, in the absence of a history of previous clinical stroke or known stroke risk factors and taking into account disease duration. METHODS Fifty-three patients with RLS < 10 y were prospectively recruited along with 44 with RLS > 10 y and 74 normal controls. A magnetic resonance imaging study was obtained from all subjects and scans were analyzed for area and volume of SVD. RESULTS There was a significant increase in SVD area in the entire group of RLS patients compared to controls (P = 0.036); this was almost entirely driven by the group with RLS > 10 y. SVD area and volume were significantly increased in patients with RLS > 10 y with respect to both controls (P < 0.0001 and P < 0.0014, respectively) and RLS < 10 y (P < 0.00022 and P < 0.003, respectively). Age, duration of RLS, and the interaction of age and duration of RLS were independent predictors of SVD disease. Duration of RLS was an independent predictor of the burden of cerebral SVD (area P < 0.00012 and volume P < 0.0025), whereas sex and insomnia were not. CONCLUSION RLS duration should be taken into account when analyzing the association between RLS and cerebrovascular disease; our data support the hypothesis that a long-lasting RLS and its accompanying periodic limb movements in sleep are a risk factor for silent SVD and perhaps for the development of clinical stroke.

Hospital mortality in primary admissions of septic patients with status epilepticus in the United States

Objective:To determine the prevalence of status epilepticus, associated factors, and relationship with in-hospital mortality in primary admissions of septic patients in the United States. Design:Cross-sectional study. Setting:Primary admissions of adult patients more than 18 years old with a diagnosis of sepsis and status epilepticus from 1988 to 2008 identified through the Nationwide Inpatient Sample. Participants:A total of 7,669,125 primary admissions of patients with sepsis. Interventions:None. Results:During the 21-year study period, the prevalence of status epilepticus in primary admissions of septic patients increased from 0.1% in 1988 to 0.2% in 2008 (p < 0.001). Status epilepticus was also more common among later years, younger admissions, female gender, Black race, rural hospital admissions, and in those patients with organ dysfunctions. Mortality of primary sepsis admissions decreased from 20% in 1988 to 18% in 2008 (p < 0.001). Mortality in status epilepticus during sepsis decreased from 43% in 1988 to 28% in 2008. In-hospital mortality after admissions for sepsis was associated with status epilepticus, older age, and Black and Native American/Eskimo race; patients admitted to a rural or urban private hospitals; and patients with organ dysfunctions. Conclusion:Our analysis demonstrates that status epilepticus after admission for sepsis in the United States was rare. Despite an overall significant reduction in mortality after admission for sepsis, status epilepticus carried a higher risk of death. More aggressive electrophysiological monitoring and a high level of suspicion for the diagnosis of status epilepticus may be indicated in those patients with central nervous system organ dysfunction after sepsis.

Association between acute sympathetic response, early onset vasospasm, and delayed vasospasm following spontaneous subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is accompanied by a marked acute sympathetic response, and evidence exists for sympathetic participation in the development of cerebral vasospasm (VS). The purpose of this observational investigation was to assess the association between acute central catecholaminergic activity, early VS and delayed VS following SAH. SAH grade 3-5 patients who received ventriculostomy, and in whom bilateral temporal transcranial insonation was performed, were enrolled. Cerebrospinal fluid (CSF) was sampled (<48 hours) and assayed for catecholamines, which were correlated to measures of early and delayed sonographic anterior circulation VS. Clinical independent predictors of early VS included age (odds ratio .946 [95% confidence interval .902-.991]), CT scan score (4.27 [1.30-14.0]) and neurogenic cardiomyopathy (6.5 [1.24-34.1]). Age (.925 [.859-.996]) and CT scan score (8.30 [1.33-5.17]) also independently predicted delayed VS. Any early VS independently predicted conventionally defined delayed VS (10.9 [2.64-45.0]), and severe delayed VS was independently predicted by any early VS (9.87 [2.45-39.7]) and by conventionally defined early VS (12.3 [2.80-54.1]). The norepinephrine:3,4-dihydroxyphenylglycol ratio (NE/DHPG) independently predicted severe delayed VS (3.38 [1.01-11.35]), for which DHPG was a negative predictor (.356 [.151-.839]). Epinephrine was a negative predictor of any early VS (.574 [.357-.921]), any delayed VS (.372 [.158-.875]), and delayed conventional VS (.402 [.200-.807]). Early and delayed VS appear to be related processes that are generally unrelated to the acute central sympathetic response following SAH. The one exception may be severe delayed VS which may be associated with noradrenergic activation.

Candida cerebral abscesses: a case report and review of the literature.

Cerebral abscess caused by Candida spp. is a rare disease, with a nonspecific presentation, little data on treatment, and generally poor outcomes. We present a case of this type of Candida infection in a 57-year-old man with a history of uncontrolled diabetes mellitus and intravenous drug abuse, and review the literature on this disease. Our patient had a good treatment outcome with liposomal amphotericin B and flucytosine, followed by oral fluconazole. Comorbidities include prior antibiotic use (52%), prior surgery (28%), malignancy (28%), stem cell or solid organ transplant (20%), prior corticosteroid use (16%), central venous catheter (CVC) insertion (10%), and burns (7%). Diagnosis requires a high index of suspicion, as clinical presentations and laboratory data can be nonspecific and difficult to differentiate from bacterial cerebral abscesses. In reviewed cases, 55% of blood cultures and 23% of cerebrospinal fluid (CSF) cultures were positive for Candida spp. and outcomes were poor, as the mortality rate of the non-autopsy cases reviewed was 69%.

Plasma Catecholamine Profile of Subarachnoid Hemorrhage Patients with Neurogenic Cardiomyopathy

Purpose: To investigate the connection between sympathetic function and neurogenic cardiomyopathy (NC), and to determine whether NC is mediated primarily by circulating adrenal epinephrine (EPI) or neuronally transmitted norepinephrine (NE), following subarachnoid hemorrhage (SAH). Methods: This is a prospective observational investigation of consecutive severe-grade SAH patients. All participants had transthoracic echocardiography and serological assays for catecholamine levels - dopamine (DA), NE and EPI - within 48 h of hemorrhage onset. Clinical and serological independent predictors of NC were determined using multivariate logistic regression analyses, and the accuracy of predictors was assessed by receiver operating characteristic (ROC) curves. Multivariate linear regression analyses were used to evaluate correlations among the catecholamines. Results: The investigation included a total of 94 subjects: the mean age was 55 years, 81% were female and 57% were Caucasian. NC was identified in approximately 10% (9/94) of cases. Univariate analyses revealed associations between NC and worse clinical severity (p = 0.019), plasma DA (p = 0.018) and NE levels (p = 0.024). Plasma NE correlated with DA levels (ρ = 0.206, p = 0.046) and EPI levels (ρ = 0.392, p < 0.001), but was predicted only by plasma EPI in bivariate [parameter estimate (PE) = 1.95, p < 0.001] and multivariate (PE = 1.89, p < 0.001) linear regression models. Multivariate logistic regression analyses consistently demonstrated the predictive value of clinical grade for NC (p < 0.05 for all analyses) except in models incorporating plasma NE, where NC was independently predicted by NE level (OR 1.25, 95% CI 1.01-1.55) over clinical grade (OR 4.19, 95% CI 0.874-20.1). ROC curves similarly revealed the greater accuracy of plasma NE [area under the curve (AUC) 0.727, 95% CI 0.56-0.90, p = 0.02] over clinical grade (AUC 0.704, 95% CI 0.55-0.86, p = 0.05) for identifying the presence or absence of NC. Conclusions: Following SAH, the development of NC is primarily related to elevated plasma NE levels. Findings implicate a predominantly neurogenic process mediated by neuronal NE (and not adrenal EPI), but cannot exclude synergy between the catecholamines.

The Incidence and Risk Factors of Associated Acute Myocardial Infarction (AMI) in Acute Cerebral Ischemic (ACI) Events in the United States

Objectives To determine the association between myocardial infarction (AMI) and clinical outcome in patients with primary admissions diagnosis of acute cerebral ischemia (ACI) in the US. Methods Data from Nationwide Inpatient Sample (NIS) was queried from 2002–2011 for inpatient admissions of patients with a primary diagnosis of ACI with and without AMI using International Classification of Diseases, Ninth Revision, Clinical Modification coding (ICD-9). A multivariate stepwise regression analysis was performed to assess the correlation between identifiable risk factors and clinical outcomes. Results During 10 years the NIS recorded 886,094 ACI admissions with 17,526 diagnoses of AMI (1.98%). The overall cumulative mortality of cohort was 5.65%. In-hospital mortality was associated with AMI (aOR 3.68; 95% CI 3.49–3.88, p≤0.0001), rTPA administration (aOR 2.39 CI, 2.11–2.71, p<0.0001), older age (aOR 1.03, 95% CI, 1.03–1.03, P<0.0001) and women (aOR 1.06, 95% CI 1.03–1.08, P<0.0001). Overall, mortality risk declined over the course of study; from 20.46% in 2002 to 11.8% in 2011 (OR 0.96, 95% CI 0.95–0.96, P<0.0001). Survival analysis demonstrated divergence between the AMI and non-AMI sub-groups over the course of study (log-rank p<0.0001). Conclusion Our study demonstrates that although the prevalence of AMI in patients hospitalized with primary diagnosis of ACI is low, it negatively impacts survival. Considering the high clinical burden of AMI on mortality of ACI patients, a high quality monitoring in the event of cardiac events should be maintained in this patient cohort. Whether prompt diagnosis and treatment of associated cardiovascular diseases may improve outcome, deserves further study.

Posterior Reversible Encephalopathy Syndrome Presenting as Opsoclonus-Myoclonus.

Opsoclonus-myoclonus may be caused by various neurological conditions and toxic-metabolic states, but typically occurs as a parainfectious or paraneoplastic manifestation. The development of opsoclonus-myoclonus has been variably attributed to lesions in the pons or cerebellum. Herein the authors describe a case of opsoclonus-myoclonus due to posterior reversible encephalopathy syndrome in which magnetic resonance imaging revealed lesions in the region of the cerebellar dentate nuclei. Clinical and radiological resolution of the opsoclonus-myoclonus and of the posterior reversible encephalopathy syndrome followed antihypertensive therapy.

Thunderclap Headache With Normal CT and Lumbar Puncture

Why? Because it’s just not that simple. Thunderclap headache, typically considered synonymous with aneurysmal subarachnoid hemorrhage (SAH), can also be a nonspecific presentation for a variety of other vascular and nonvascular central nervous system processes. In addition to SAH, a large number of conditions can present with an explosive headache and a normal head CT (Table).1,2 For most of these conditions the diagnosis rests on the performance of additional investigations. Cervicocranial vascular imaging studies such as magnetic resonance angiography, CT angiography, or catheter angiography are essential for diagnosing cervical or cerebral arterial dissections, vasospasm, arterial occlusions (when early CT demonstrates no evidence of ischemia), vasculitis, and aneurysms. MR venography, CT venography, and venous phase angiography may confirm dural sinus thrombosis or cortical vein thrombosis. Finally, routine MRI can readily identify hemorrhagic or ischemic pituitary apoplexy as well as posterior circulation vasogenic edema from hypertensive crises, and fat-suppression techniques have become the gold-standard for visualizing …

A comprehensive analysis of the relationship between ACA velocities and ACA infarction following aneurysmal subarachnoid hemorrhage

PURPOSE To evaluate the relationship between anterior cerebral artery (ACA) velocities (and ancillary parameters) and ACA infarction following aneurysmal subarachnoid hemorrhage (aSAH), and to examine the factors that influence velocities. METHODS Retrospective investigation of 500 consecutive aSAH patients. ACA mean velocities (Vm) were evaluated by daily transcranial ultrasound during the early (days 1-4) and late (days 5-20) periods posthemorrhage. Presence and timing of acute ACA infarctions were identified by serial retrospective review of cerebral computerized tomography (CT) scans. Predictors of ACA velocities were identified and compared to predictors of vasospasm and infarction from the literature. RESULTS Decreased velocities on the day of infarction were observed in infarct-positive vessels when compared to infarct-negative vessels. ACA velocity increases, ipsilateral/contralateral ACA velocity ratios, and ACA velocity ranges, were inaccurate in anticipating infarction. Decreased ACA index velocities were moderately accurate in anticipating ACA infarction during the early [Vm<60cms/s], late [Vm<70cms/s] and overall [Vm<70cms/s] time periods. Decreased index velocities also independently predicted infarction during all time periods. ACA velocities were most consistently predicted by age, race, hemorrhage quantity on CT, and ACA/ACom (anterior communicating artery) aneurysm location. CONCLUSIONS ACA velocity increases and ancillary parameters do not relate to the development of infarction, whereas velocity decreases are moderately accurate in anticipating infarction. Predictors of velocity increases generally coincide with those of vasospasm, whereas predictors of velocity decreases coincide more with those of infarction following aSAH.